HLA-DRB1 alleles influence clinical phenotypes in Japanese patients with ulcerative colitis
HLA-DRB1 alleles influence clinical phenotypes in Japanese patients with ulcerative colitis
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DOI：
10.1111/j.1399-0039.2008.01031.x
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发表时间：
2008-05-01
期刊：
影响因子：
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通讯作者：
Shimosegawa, T.
中科院分区：
文献类型：
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作者：
Matsumura, Y.;Kinouchi, Y.;Shimosegawa, T.
人类白细胞抗原(人类白细胞抗原)区域与炎症性肠病的疾病易感性有关，已有多项连锁和关联研究。据报道，在高加索人中，人类白细胞抗原DRB1基因可用于确定溃疡性结肠炎(UC)的临床表型。其他人和我们先前报道，在日本人群中，人类白细胞抗原-DRB1*1502与UC密切相关。然而，人类白细胞抗原-DRB1在日本UC的临床表型中的作用尚未阐明。本研究的目的是确定人类白细胞抗原-DRB1等位基因是否与日本UC患者的临床表型相关。共纳入353例UC患者。根据性别、确诊年龄、疾病程度、需要类固醇治疗或需要手术治疗，患者被分成不同的亚组。疾病延伸至直肠以外(左侧广泛UC)的患者HLADRB1*08等位基因频率显著高于直肠炎组[优势比(OR)=2.2，Pc=0.043]。年龄在40岁及以上的UC患者HLADRB1*09等位基因频率显著高于40岁前确诊的UC患者(OR=2.31，Pc=0.022)。除这些正相关外，其他亚组间的等位基因频率无显著差异。我们得出结论：在日本，人类白细胞抗原DRB1*09与发病年龄有关，而人类白细胞抗原-DRB1*08与溃疡性结肠炎的病情有关。这些结果表明，HLADRB1不仅与日本人UC的总体易感性有关，而且还与临床表型有关。
The human leukocyte antigen (HLA) region has been implicated in the disease susceptibility of inflammatory bowel disease by several linkage and association studies. In Caucasians, HLA-DRB1 has been reported to determine the clinical phenotypes of ulcerative colitis (UC). Others and we previously reported that HLA-DRB1*1502 was strongly associated with UC in the Japanese population. However, the contribution of HLA-DRB1 to the clinical phenotypes in Japanese UC has not been elucidated yet. The aim of this study was to determine whether HLA-DRB1 alleles were associated with the clinical phenotypes in Japanese patients with UC. A total of 353 patients with UC were recruited. Patients were classified into subgroups by sex, age at diagnosis, disease extent, need for steroid therapy or need for surgical treatment. The allele frequency of HLA-DRB1*08 was significantly higher in patients whose disease extended beyond the rectum (left-sided and extensive UC) than in those with proctitis [odds ratio (OR) = 2.20, Pc = 0.043). The allele frequency of HLA-DRB1*09 was significantly higher in patients with UC diagnosed at the age of 40 years or older than in those with UC diagnosed before the age of 40 years (OR = 2.31, Pc = 0.022). Besides these positive associations, no significant differences were found in the allele frequencies between the other subgroups. We conclude that HLA-DRB1*09 is associated with the age at diagnosis and HLA-DRB1*08 is associated with the disease extent of UC in Japanese. These results indicate that HLA-DRB1 is not only associated with the overall UC susceptibility but also associated with the clinical phenotypes in Japanese.